2023
Top advances of the year: Neuro‐oncology
Barden M, Omuro A. Top advances of the year: Neuro‐oncology. Cancer 2023, 129: 1467-1472. PMID: 36825454, DOI: 10.1002/cncr.34711.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBrain tumorsRecent phase 3 trialAnti-PD-1 immunotherapyCentral nervous system dysfunctionSingle-agent pembrolizumabHigh-dose chemotherapyPhase 3 trialPrimary CNS lymphomaStem cell transplantationLong-term outcomesLimited therapeutic optionsNervous system dysfunctionOngoing clinical trialsClinical trial landscapeDrug Administration approvalBRAF V600E mutationExcellent disease controlConsolidation therapyCNS lymphomaImproved survivalLeptomeningeal metastasesTherapeutic optionsCell transplantationCraniospinal irradiationPatient populationMulticenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefit
2022
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter
Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro-Oncology 2022, 24: 1935-1949. PMID: 35511454, PMCID: PMC9629431, DOI: 10.1093/neuonc/noac116.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalMGMT promoterBaseline corticosteroidsTreatment-related adverse event ratesImmune checkpoint inhibitor nivolumabNew safety signalsPhase III trialsAdverse event ratesCheckpoint inhibitor nivolumabCare radiotherapyInhibitor nivolumabPrimary endpointIII trialsSame regimenExperience recurrenceNivolumabSafety signalsPlaceboPatientsRadiotherapyTemozolomideEvent ratesMonthsPhase IIIImmune-checkpoint inhibitors for glioblastoma: what have we learned?
Omuro A. Immune-checkpoint inhibitors for glioblastoma: what have we learned? Arquivos De Neuro-Psiquiatria 2022, 80: 266-269. PMID: 35976319, PMCID: PMC9491432, DOI: 10.1590/0004-282x-anp-2022-s129.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsRecurrent glioblastomaBrain tumorsRandomized phase 3 trialCommon malignant primary brain tumorPost-treatment tumor samplesMalignant primary brain tumorSuccessful immunotherapeutic approachesPhase 3 trialPhase 1 studySelection of patientsT cell dysfunctionNew safety concernsHigh mutational burdenPrimary brain tumorsCheckpoint inhibitorsRadiographic responseImmunotherapeutic approachesPD-L1Survival improvementImmunologic responseTherapeutic optionsClinical trialsCNS microenvironmentCell dysfunctionRadiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial
Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bähr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris AG, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro-Oncology 2022, 25: 123-134. PMID: 35419607, PMCID: PMC9825306, DOI: 10.1093/neuonc/noac099.Peer-Reviewed Original ResearchConceptsOverall survivalUnmethylated MGMT promoterMedian OSPrimary endpointInternational randomized phase III trialTreatment-related adverse event ratesMedian progression-free survivalRandomized phase III trialMGMT promoterEfficacy of nivolumabLonger median OSMedian overall survivalNew safety signalsProgression-free survivalAddition of temozolomideAdverse event ratesPhase III trialsUse of temozolomideStandard of careStudy treatment armsImproved OSIII trialsTreatment armsStandard radiotherapyNivolumabMachine Learning in Differentiating Gliomas from Primary CNS Lymphomas: A Systematic Review, Reporting Quality, and Risk of Bias Assessment
Petersen G, Shatalov J, Verma T, Brim WR, Subramanian H, Brackett A, Bahar RC, Merkaj S, Zeevi T, Staib LH, Cui J, Omuro A, Bronen RA, Malhotra A, Aboian MS. Machine Learning in Differentiating Gliomas from Primary CNS Lymphomas: A Systematic Review, Reporting Quality, and Risk of Bias Assessment. American Journal Of Neuroradiology 2022, 43: 526-533. PMID: 35361577, PMCID: PMC8993193, DOI: 10.3174/ajnr.a7473.Peer-Reviewed Original ResearchConceptsMachine learning-based methodsLearning-based methodsBalanced data setData setsVector machine modelMachine learningClassification algorithmsMachine modelMachineAlgorithmData basesPrediction modelPromising resultsPrimary CNS lymphomaPrediction model study RiskRisk of biasRadiomic featuresClassifierSetCNS lymphomaWebLearningFeaturesQualitySystematic reviewUsing Adversarial Images to Assess the Robustness of Deep Learning Models Trained on Diagnostic Images in Oncology
Joel MZ, Umrao S, Chang E, Choi R, Yang DX, Duncan JS, Omuro A, Herbst R, Krumholz HM, Aneja S. Using Adversarial Images to Assess the Robustness of Deep Learning Models Trained on Diagnostic Images in Oncology. JCO Clinical Cancer Informatics 2022, 6: e2100170. PMID: 35271304, PMCID: PMC8932490, DOI: 10.1200/cci.21.00170.Peer-Reviewed Original Research
2021
T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies
Jansen JA, Omuro A, Lucca LE. T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies. Current Opinion In Neurology 2021, 34: 827-833. PMID: 34569985, PMCID: PMC8595795, DOI: 10.1097/wco.0000000000000988.Peer-Reviewed Original ResearchConceptsT cell dysfunctionTumor-infiltrating T cellsT cellsCell dysfunctionFuture immunotherapy strategiesCervical lymph nodesTumor-derived antigensImmune checkpoint blockadeCentral nervous systemHomeostatic brainSuccessful immunotherapyCheckpoint blockadeImmunotherapy strategiesLymph nodesTumor rejectionImmune surveillanceImmune responseMouse modelBrain tumorsLymphatic drainageNervous systemSolid tumorsDysfunctionSingle-cell RNA sequencingNatural historyComparison of radiomic feature aggregation methods for patients with multiple tumors
Chang E, Joel MZ, Chang HY, Du J, Khanna O, Omuro A, Chiang V, Aneja S. Comparison of radiomic feature aggregation methods for patients with multiple tumors. Scientific Reports 2021, 11: 9758. PMID: 33963236, PMCID: PMC8105371, DOI: 10.1038/s41598-021-89114-6.Peer-Reviewed Original ResearchConceptsCox proportional hazards modelCox proportional hazardsProportional hazards modelBrain metastasesRadiomic featuresHazards modelProportional hazardsStandard Cox proportional hazards modelMultifocal brain metastasesMultiple brain metastasesNumber of patientsPatient-level outcomesHigher concordance indexRadiomic feature analysisRandom survival forest modelSurvival modelsDifferent tumor volumesMultifocal tumorsCancer outcomesMultiple tumorsMetastatic cancerConcordance indexTumor volumePatientsTumor types
2020
Genetic characterization of an aggressive optic nerve pilocytic glioma
Hong CS, Fliney G, Fisayo A, An Y, Gopal PP, Omuro A, Pointdujour-Lim R, Erson-Omay EZ, Omay SB. Genetic characterization of an aggressive optic nerve pilocytic glioma. Brain Tumor Pathology 2020, 38: 59-63. PMID: 33098465, PMCID: PMC7585354, DOI: 10.1007/s10014-020-00383-x.Peer-Reviewed Original ResearchConceptsOptic nerve gliomaLeft optic nerve sheathLeft-sided visual lossSporadic adult casesOptic nerve sheathNeurofibromatosis type 1 syndromeType 1 syndromeWhole-exome sequencingEmpiric managementVisual lossFocal radiotherapyOptic nervePediatric populationNerve sheathOpen biopsyAdult casesBiopsy specimenBenign histopathologyClinical prognosticationPilocytic astrocytomaComplex tumorsActionable targetsVisual pathwayAdult populationTumor progressionA phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma
Gilbert MR, Yuan Y, Wu J, Mendoza T, Vera E, Omuro A, Lieberman F, Robins HI, Gerstner ER, Wu J, Wen PY, Mikkelsen T, Aldape K, Armstrong TS. A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma. Neuro-Oncology 2020, 23: 468-477. PMID: 33085768, PMCID: PMC7992893, DOI: 10.1093/neuonc/noaa240.Peer-Reviewed Original ResearchConceptsProgression-free survivalDose-dense temozolomideMedian progression-free survivalAdult patientsObjective responseSymptom burdenClinical trialsRecurrent ependymomaMD Anderson Symptom Inventory-Brain TumorProspective phase II clinical trialMedian Karnofsky performance statusPhase II clinical trialDemonstrated clinical activityModerate-severe painPatients age 18Phase II studyKarnofsky performance statusProspective clinical trialsSpinal cord tumorsStandard medical treatmentPrimary outcome measureSpinal cord ependymomasDisease-related symptomsExpression of ErbB2Daily lapatinibConsolidation Therapy in Primary Central Nervous System Lymphoma
Kim P, Omuro A. Consolidation Therapy in Primary Central Nervous System Lymphoma. Current Treatment Options In Oncology 2020, 21: 74. PMID: 32725379, DOI: 10.1007/s11864-020-00758-4.Peer-Reviewed Original ResearchConceptsWhole-brain radiation therapyCentral nervous system lymphomaLong-term remissionNervous system lymphomaConsolidation therapyInduction therapyPerformance statusTransplant candidatesSystem lymphomaOpinion statementPrimary central nervous system lymphomaPrimary central nervous system lymphomaAutologous stem cell transplantTransplant-related mortality riskAdequate organ functionFavorable performance statusInitial induction therapyECOG performance statusHigh-dose cytarabineHigh-dose methotrexateHigh-dose chemotherapyStem cell transplantEnd of inductionHigh response rateCurative intentMyeloablative regimenEffect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma
Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma. JAMA Oncology 2020, 6: 1003-1010. PMID: 32437507, PMCID: PMC7243167, DOI: 10.1001/jamaoncol.2020.1024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAntineoplastic Agents, ImmunologicalBevacizumabBrain NeoplasmsDNA Modification MethylasesDNA Repair EnzymesFemaleGlioblastomaHumansImmune Checkpoint InhibitorsMaleMiddle AgedNeoplasm Recurrence, LocalNivolumabProgrammed Cell Death 1 ReceptorTemozolomideTreatment OutcomeTumor Suppressor ProteinsYoung AdultConceptsTreatment-related adverse eventsPhase 3 clinical trialsPrimary end pointOverall survivalRecurrent glioblastomaClinical trialsMedian OSGrade 3/4 treatment-related adverse eventsRandomized phase 3 clinical trialSingle-agent PD-1 blockadeEnd pointEffects of nivolumabUnacceptable toxic effectsMedian overall survivalObjective response ratePD-1 blockadeOverall patient populationImmune checkpoint blockadeData cutoffAdverse eventsCheckpoint blockadeFirst recurrenceInhibitor therapyClinical outcomesSafety profileCerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer
Malani R, Fleisher M, Kumthekar P, Lin X, Omuro A, Groves MD, Lin NU, Melisko M, Lassman AB, Jeyapalan S, Seidman A, Skakodub A, Boire A, DeAngelis LM, Rosenblum M, Raizer J, Pentsova E. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer. Journal Of Neuro-Oncology 2020, 148: 599-606. PMID: 32506369, PMCID: PMC7438284, DOI: 10.1007/s11060-020-03555-z.Peer-Reviewed Original ResearchConceptsLeptomeningeal metastasesCSF cytologyCSF CTCsCTC enumerationCerebrospinal fluidIT trastuzumabPhase I/II dose escalation trialCentral nervous system compartmentTumor cellsHER2/neu positivityHER2/neu expressionDose-escalation trialHER2-positive cancersIntrathecal trastuzumabEscalation trialRadiographic responseTumor burdenPositive cancersNeu expressionNeu positivityConclusionOur studyPatientsDay 1Epithelial cancersCancerPhase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma
Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Annals Of Clinical And Translational Neurology 2020, 7: 429-436. PMID: 32293798, PMCID: PMC7187704, DOI: 10.1002/acn3.51009.Peer-Reviewed Original ResearchConceptsRecurrent malignant gliomaDose-limiting toxicityMTOR inhibitor temsirolimusMalignant gliomasAkt inhibitor perifosinePhase I clinical trialDose level 3Dose level 7Phase II doseSynergistic anti-tumor effectKarnofsky performance statusPhase I trialDeadly primary brain cancerPI3K/Akt/mTOR axisPrimary brain cancerAkt/mTOR axisAnti-tumor effectsPotential therapeutic targetMost malignant gliomasPrior therapyTemsirolimus dosePerformance statusI trialIntracerebral hemorrhageCombined therapyErdheim-Chester disease among neuroinflammatory syndromes: the case for precision medicine
de la Fuente MI, Rosenblum MK, Diamond EL, Tabar VS, Omuro A. Erdheim-Chester disease among neuroinflammatory syndromes: the case for precision medicine. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e686. PMID: 32123043, PMCID: PMC7136060, DOI: 10.1212/nxi.0000000000000686.Peer-Reviewed Original Research
2019
Complications associated with immunotherapy for brain metastases.
Tran TT, Jilaveanu LB, Omuro A, Chiang VL, Huttner A, Kluger HM. Complications associated with immunotherapy for brain metastases. Current Opinion In Neurology 2019, 32: 907-916. PMID: 31577604, PMCID: PMC7398556, DOI: 10.1097/wco.0000000000000756.Peer-Reviewed Original ResearchConceptsBrain metastasesNeurologic toxicityImmune therapyPhase 2 clinical trialCheckpoint inhibitor therapyImmune checkpoint inhibitorsMultiple phase 2 clinical trialsTreatment-related morbidityBrain metastatic diseaseSymptomatic edemaCheckpoint inhibitorsAdverse eventsDurable responsesMedian survivalMetastatic diseaseInhibitor therapyMore patientsIntracranial activityPatient groupRadiation necrosisClinical trialsTherapy trialsMultidisciplinary teamMetastasisPatientsApplications of artificial intelligence in neuro-oncology.
Aneja S, Chang E, Omuro A. Applications of artificial intelligence in neuro-oncology. Current Opinion In Neurology 2019, 32: 850-856. PMID: 31609739, DOI: 10.1097/wco.0000000000000761.Peer-Reviewed Original ResearchConceptsArtificial intelligenceArtificial intelligence algorithmsNatural language processingAmount of dataIntelligence algorithmsLanguage processingIntelligenceNeuro-oncologyImage analysisApplicationsAlgorithmRisk stratificationFuture innovationsTreatment responseBrain tumorsClinical practiceClassificationRecent applicationsProcessingSignificant promiseChallengesDetectionImaging biomarkers for brain metastases: more than meets the eye
Aneja S, Omuro A. Imaging biomarkers for brain metastases: more than meets the eye. Neuro-Oncology 2019, 21: 1493-1494. PMID: 31777936, PMCID: PMC6917408, DOI: 10.1093/neuonc/noz193.Peer-Reviewed Original ResearchLongitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation
Correa DD, Braun E, Kryza-Lacombe M, Ho KW, Reiner AS, Panageas KS, Yahalom J, Sauter CS, Abrey LE, DeAngelis LM, Omuro A. Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation. Journal Of Neuro-Oncology 2019, 144: 553-562. PMID: 31377920, PMCID: PMC7392129, DOI: 10.1007/s11060-019-03257-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsCognitionCombined Modality TherapyCranial IrradiationFemaleFollow-Up StudiesHematopoietic Stem Cell TransplantationHumansInduction ChemotherapyLongitudinal StudiesLymphomaMaleMiddle AgedPrognosisQuality of LifeSurvival RateTransplantation, AutologousYoung AdultConceptsWhole brain radiotherapyReduced-dose whole-brain radiotherapyPrimary central nervous system lymphomaHDC-ASCTCortical atrophyAttention/executive functionPCNSL patientsAutologous stem cell transplantConsolidation whole-brain radiotherapyAutologous stem cell transplantationCentral nervous system lymphomaCognitive functionIntroductionThe standard treatmentLongitudinal cognitive assessmentsProgression-free patientsHigh-dose chemotherapyMethotrexate-based chemotherapyLong-term remissionPrimary CNS lymphomaNervous system lymphomaStem cell transplantStem cell transplantationBrain structure abnormalitiesPost-induction chemotherapyWhite matter disease